title: Urinary phthalates from 168 girls and boys measured twice a year during a 5-year period: associations with adrenal androgen levels and puberty.
abstract: BACKGROUND
  Little is known about the possible deleterious effects of phthalate exposure on endogenous sex steroid levels in children.
  
  
  OBJECTIVE
  Our objective was to investigate whether urinary phthalate metabolite levels are associated with circulating adrenal androgen levels and age at puberty.
  
  
  METHODS
  This was a longitudinal study of 168 healthy children (84 girls) examined every 6 months for 5 years. Serum levels of dehydroepiandrostenedione sulfate (DHEAS), Δ4-androstenedione, testosterone, and urinary morning excretion of 14 phthalate metabolites, corresponding to 7 different phthalate diesters were determined. A variation in urinary excretion of phthalates was evident in each child, which made a mean of repetitive samples more representative for long-term excretion than a single determination.
  
  
  RESULTS
  We found that girls with excretion of monobutyl phthalate isomers (MBP) and di(2-ethylhexyl) phthalate metabolites above the geometric group mean (795 and 730 ng/kg, respectively) had lower levels of DHEAS and Δ4-androstenedione, although statistically significant only at 13 years of age. In boys, we found that excretion of monobenzyl phthalate above the geometric group mean (346 ng/kg) was associated with lower levels of DHEAS at 11 years of age but higher levels of testosterone at 13 years of age. The same trend was observed for MBP excretion, albeit not statistically significant. A lower age at pubarche was observed in boys with excretion of MBP above the geometric group mean (11.0 vs 12.3 years, P = 0.005).
  
  
  CONCLUSIONS
  Our data indicate that exposure to dibutyl phthalate isomers (DBP) (in girls) and butylbenzyl phthalate (in boys) are negatively associated with adrenal androgen levels and in boys positively associated with testosterone level at 13 years of age. High exposure to DBP was associated with earlier age at pubarche in boys. In girls, no associations between phthalate exposure and age at pubertal milestones were observed.
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. annette.mouritsen@rh.regionh.dk
authors.forename: A
authors.initials: A
authors.lastname: Mouritsen
authors.forename: H
authors.initials: H
authors.lastname: Frederiksen
authors.forename: K
authors.initials: K
authors.lastname: Sørensen
authors.forename: L
authors.initials: L
authors.lastname: Aksglaede
authors.forename: C
authors.initials: C
authors.lastname: Hagen
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
authors.forename: K M
authors.initials: KM
authors.lastname: Main
authors.forename: A M
authors.initials: AM
authors.lastname: Andersson
authors.forename: A
authors.initials: A
authors.lastname: Juul
mesh_terms: D000293:Adolescent; D000735:Androstenedione / Q000097:blood; D002648:Child; D002675:Child, Preschool; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003718:Denmark; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000652:urine*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010795:Phthalic Acids / Q000652:urine*; D011627:Puberty / Q000097:blood / Q000652:urine*; D013739:Testosterone / Q000097:blood
chemical_list: D004785:Environmental Pollutants; D010795:Phthalic Acids; D013739:Testosterone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate